The enzymatic initiation of DNA repair of specific forms of damage-5,6-dihydrodihydroxythymine, pyrimidine dimers and interstrand cross-links -will be investigated. Substrate supercoiled DNA will be prepared containing only one type of such damage. Repair endonucleases will be assayed by measuring the conversion of the damaged supercoiled DNA to the nicked form. These activities in normal cells will be compared to those in xeroderma pigmentosum and Fanconi's anemia, genetically transmitted diseases with high incidences of cancer. Deficiencies will be explored by standard biochemical techniques, including purification of these enzyme activities. The results will elucidate the mechanisms of initiation of excision-repair of such DNA damage in normal cells and its defects in human diseases that lead to the development of cancer.